Old Blood Impairs Young Brains

Brain boost: Normally the brains of older mice (left) grow fewer new neurons (dark brown) than when the animals were younger. But when older mice shared the blood of younger mice, their neurons grew more robustly (right).

It’s a cliché of vampire tales that young blood is preferable to old, but a new study suggests there’s some truth to it.

A paper published today in Nature finds that when younger mice are exposed to the blood of older mice, their brain cells behave more like those found in aging brains, and vice versa. The researchers who carried out the work also uncovered chemical signals in aged blood that can dampen the growth of new brain cells, suggesting that the decline in brain function with age could be caused in part by blood-borne factors rather than an intrinsic failure of brain cells.

To arrive at the discovery, the researchers studied pairs of old and young mice that were literally joined at the hip. They used a technique called parabiosis, in which two mice are surgically joined together along the flank, which causes them to develop a shared circulatory system. The technique has been used to study the development of the blood system, and more recently has been used to investigate the effects of age by joining old and young mice.

Lead author Tony Wyss-Coray, a neuroscientist at Stanford University, says that five weeks after creating these May-December pairings, “we found striking effects both on the young and old brains.” The young mice had a reduction in the production of new neurons (neurogenesis), an increase in brain inflammation, and less activity in synapses connecting neurons.

The older mice, in contrast, had an increase in new neurons, less inflammation, and greater activity at synapses. “You could almost call this a rejuvenation effect,” Wyss-Coray says.

To see whether the effect could influence behavior, they injected, in separate experiments, young mice with plasma from older mice and vice versa, and found that old plasma impaired the younger animals’ ability to perform learning and memory tasks, whereas young plasma improved the abilities of older mice.

Blood cells from one mouse cannot travel into the brain of the other because of the blood-brain barrier, so the team concluded that free-floating molecules in the blood, capable of passing through, must be responsible for the effects. By comparing more than 60 chemokines—chemical messengers secreted by cells that circulate in the blood—the researchers identified several associated with the detrimental effect of old blood. Administering one of these chemicals, called CCL11, to young mice dampened neurogenesis and impaired learning and memory. CCL11 has been studied for its role in allergies and asthma, but it’s not clear how it influences neurons.

Richard Ransohoff, director of the Neuroinflammation Research Center at the Cleveland Clinic, who was not involved with the work, says that the work is intriguing in the context of a study that last year linked neurogenesis to the ratio of two different types of immune cells in the blood. Both findings are “very, very surprising,” he says, and suggest that “the process of neurogenesis can be affected from outside the brain.” Because stem cells that give rise to new neurons “live in a microenvironment, and that environment is very intimately associated with blood vessels,” he says, these cells may be influenced by chemicals that travel through the blood, including signals from the immune system.

Wyss-Coray says that the group will continue investigating whether specific blood factors cause cognitive decline with age—or offer protective effects in younger brains. Ransohoff also points out that such factors could be useful as biomarkers for neurogenesis and other signs of brain health, since the blood is vastly more accessible than the brain.